salvianolic-acid-B and Necrosis

Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.

Topics: Animals; Apoptosis; Benzofurans; Cardiotonic Agents; Chemokine CCL5; Down-Regulation; Drug Therapy, Combination; Fibroblasts; Ginsenosides; Interleukin-1beta; Male; Membrane Potential, Mitochondrial; Myocardial Reperfusion Injury; Myocytes, Cardiac; Necrosis; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Insufficient angiogenesis and microcirculatory intravascular clotting have been implicated in the pathophysiology of skin flap failure. Salvianolic acid B (Sal B), isolated from Salvia miltiorrhiza, has been reported to enhance angiogenesis in vitro. This study was aimed to determine the efficacy of Sal B on ischemia-reperfusion injury of the skin flap in Sprague-Dawley rats. Sal B was administered intraperitoneally 2 h before operation, and on the 2nd and 4th days after surgical elevation of an extended epigastric adipocutaneous flap (5 x 7 cm) in ketamine-anesthetized rats. Flap ischemia was achieved by ligating the right superficial epigastric artery and vein and clamping the left superficial epigastric artery and vein for 3 h and then released. Percentage of flap necrosis area (FNA) and plasma levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and malondialdehyde were measured at 7 days after the operation. Animals were divided into six groups, including: vehicle, Sal B low dose (5 mg/kg), Sal B high dose (50 mg/kg) and each with [mesh(+)] or without mesh [mesh(-)] placement. In the three groups with mesh(+), FNA in control flaps was 53.7 +/- 6.9%, whereas low-dose and high-dose Sal B significantly improved flap survival with FNA 27.4 +/- 3.8% and 25.3 +/- 4.3%, respectively (P < 0.05, one-way ANOVA). In the three groups with mesh(-), control flaps were 35.9 +/- 4.5%, whereas high-dose Sal B also significantly improved flap survival with FNA 17.9 +/- 4.7% (P < 0.05, one-way ANOVA). There were no differences in aspartate aminotransferase, alanine aminotransferase, creatinine, or malondialdehyde between groups. We conclude that Sal B attenuates ischemia-reperfusion injury of skin flap, and provides therapeutic potential in reconstructive plastic surgery.

Topics: Animals; Benzofurans; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; Gene Expression; In Vitro Techniques; Kidney; Liver; Male; Malondialdehyde; Matrix Metalloproteinase 2; Necrosis; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Skin; Surgical Flaps; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2